Breast Cancer is the most common type of cancer that occurs in women in the US, and it ranks as the second leading cause of cancer death after lung cancer. About 15-20% of breast cancers are classified as “triple negative” (TNBC), a subtype that lacks clinical expression of estrogen receptor-alpha, progesterone receptor and HER-2 overexpression or lacks clinical expression of ERα, progesterone receptor and HER2 receptor or lacks immunohistochemical expression of ERα, progesterone receptor and HER-2 receptor overexpression. These patients will face limited and often ineffective therapeutic options. Thus, there is an urgent need to develop new and more effective therapies for this deadly subtype of breast cancer. Triple-negative breast cancer (TNBC) cannot be treated with current endocrine or HER-2 targeted therapies (11). TNBC occurs in about 15-20% of breast cancers, yet accounts for nearly half of all breast cancer deaths. It is associated with a significantly higher probability of relapse and worse overall survival in the first few years after diagnosis when compared with other breast cancer subtypes (12). This is observed despite its high sensitivity to chemotherapy. Although initially responsive to some chemotherapies, TNBCs tend to relapse early and metastasize, leading to poor patient survival.
Pancreatic carcinoma is a highly lethal disease and the fourth-leading cause for cancer death in men and women in the US (1). The overall 5-year survival rate is approximately 4%. Conventional treatment approaches (chemotherapy, radiation, surgery or combinations of these modalities) have had little impact on the course of this disease. Surgical resection is the only chance at cure, but most patients present with advanced, unresectable disease (2,3). Since effective therapies are largely lacking, it is clear that new therapeutic approaches to treat pancreatic cancer are urgently needed. Metformin (1,1-dimethyl-biguanide hydrochloride) is a widely prescribed antihyperglycemic drug used as first-line therapy for diabetes mellitus type 2, and is now reported to have antitumor efficacy in pancreatic cancer (4-7). The primary systemic effect of metformin is to lower blood glucose, but it also reduces hyperinsulinemia associated with insulin resistance. Provided herein are solutions to these and other problems in the art.